The present invention relates to microfluidic devices and the manipulation of fluid flow within those devices. These devices are useful in various biological and chemical systems, as well as in combination with other liquid-distribution devices.
There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. In particular, microfluidic systems allow complicated biochemical reactions to be carried out using very small volumes of liquid. These miniaturized systems increase the response time of the reactions, minimize sample volume, and lower reagent cost.
Traditionally, microfluidic systems have been constructed in a planar fashion using silicon fabrication techniques. Representative systems are described, for example, by Manz, et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). These publications describe microfluidic devices constructed using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of this device to provide closure.
More recently, a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. In one such method, a negative mold is first constructed, and plastic or silicone is then poured into or over the mold. The mold can be constructed using a silicon wafer (see, e.g., Duffy, et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick, et al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices. Some molding facilities have developed techniques to construct extremely small molds. Components constructed using a lithography, electroplating and molding (LIGA) technique have been developed (see, e.g., Schomburg, et al., Journal of Micromechanical Microengineering (1994) 4: 186-191). Other approaches combine LIGA and a hot-embossing technique. Imprinting methods in polymethylmethacrylate (PMMA) have also been demonstrated (see, e.g., Martynova, et al., Analytical Chemistry (1997) 69: 4783-4789). However, these techniques do not lend themselves to rapid prototyping and manufacturing flexibility. Additionally, these techniques are limited to planar structures. Moreover, the tool-up costs for both of these techniques are quite high and can be cost-prohibitive.
Generally, the mixing of fluids in a microfluidic system is problematic, since the fluid flow within these devices is not turbulent. Some microfluidic mixing devices have been constructed in substantially planar microfluidic systems where the fluids are allowed to mix through diffusion (see Bokenkamp, et al., Analytical Chemistry (1998) 70(2): 232-236. In these systems, the fluids only mix at the interface of the fluids, which is commonly small relative to the overall volume of the fluids. Thus, very little mixing occurs.
Alternative mixing methods have been developed based on electrokinetic flow. Such devices are complicated, requiring electrical contacts within the system. Additionally such systems only work with charged fluids, or fluids containing electrolytes. Finally, these systems require voltages that are sufficiently large that water is electrolyzed, which means bubble formation is a problem and samples cannot be easily collected without being destroyed.
There is, thus, a need for a robust mixing device capable of thoroughly mixing a wide variety of fluids in a microfluidic environment in a controlled manner at relatively high speed.
In a first separate aspect of the invention, a microfluidic separator includes an inlet channel defined through the entire thickness of a first stencil layer, a first outlet channel defined through the entire thickness of a second stencil layer, a second outlet channel defined through the entire thickness of a third stencil layer, and an overlap region permitting fluid to be communicated from the inlet channel to both the first outlet channel and the second outlet channel. The first stencil layer is disposed between the second stencil layer and the third stencil layer.
In a second separate aspect of the invention, a microfluidic separator includes an inlet channel defined through the entire thickness of a first device layer, a second device layer disposed above the first device layer and defining a first outlet channel, and a third device layer disposed below the first device layer and defining a second outlet channel. The first device layer terminates in an overlap region, with both the second device layer and the third device layer being in fluid communication with the overlap region.
In another aspect, any of the foregoing aspects may be combined for additional advantage.
These and other aspects and objects of the present invention will become apparent to one skilled in the art upon reviewing the description, drawings, and appended claims.